Mechanisms and factors in embryonic stem cell self-renewal

Abstract

Embryonic stem (ES) cells are attracting renewed attention because their capacity to differentiate into cellular derivatives of all three primary germ layers suggests that they could be a source of cells for therapeutic alleviation of disease. This differentiative capacity, termed pluripotency, can be restrained during ES cell culturein vitro with the cells exhibiting an apparently unlimited capacity for symmetrical self-renewing divisions. A thorough understanding of self-renewal is essential if ES cells are to be fully exploited for therapeutic ends. Intrinsic self-renewal determinants include the homeodomain proteins Oct4 and Nanog. Increased Nanog expression alleviates the requirement for BMP and gp130 receptor stimulation and allows factor-independent ES cell self-renewal. Fusions between Nanog and GFP indicate that Nanog is localised to the cell nucleus consistent with a role as a transcriptional regulator. Mapping of the major transcription initiation site of Nanog paves the way towards identification of the factor(s) that direct Nanog gene expression and thus determine the pluripotent state.